Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma

Supriya Srivastava, Bhavin Thakkar, Khay Guan Yeoh, Khek Yu Ho, Ming Teh, Richie Soong, Manuel Salto-Tellez

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p < 0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.
Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalVirchows Archiv
Issue number5
Early online date06 Mar 2015
Publication statusPublished - May 2015


  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular
  • Cell Hypoxia
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis
  • Wnt Signaling Pathway


Dive into the research topics of 'Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this